Faculty Bibliography

BACKGROUND/OBJECTIVES/OBJECTIVE:Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is rapidly becoming the most prevalent form of chronic liver disease in both pediatric and adult populations. It encompasses a wide spectrum of liver abnormalities, ranging from simple fat accumulation to severe conditions such as inflammation, fibrosis, cirrhosis, and liver cancer. Major risk factors for MASLD include obesity, insulin resistance, type 2 diabetes, and hypertriglyceridemia. METHODS:This narrative review employed a comprehensive search of recent literature to identify the latest studies on the relationship between MAFLD and obesity, the health consequences and the latest treatment options to prevent long-term damage to the liver and other organs. Additionally, the article presents perspectives on diagnostic biomarkers. RESULTS:Childhood obesity is linked to a multitude of comorbid conditions and remains a primary risk factor for adult obesity. This abnormal fat accumulation is known to have long-term detrimental effects into adulthood. Scientific evidence unequivocally demonstrates the role of obesity-related conditions, such as insulin resistance, dyslipidemia, and hyperglycemia, in the development and progression of MASLD. Oxidative stress, stemming from mitochondrial dysfunction, is a leading factor in MASLD. This review discusses the interconnections between oxidative stress, obesity, dyslipidemia, and MASLD. CONCLUSIONS:Atherogenic dyslipidemia, oxidative stress, inflammation, insulin resistance, endothelial dysfunction, and cytokines collectively contribute to the development of MASLD. Potential treatment targets for MASLD are focused on prevention and the use of drugs to address obesity and elevated blood lipid levels.

While the advent of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory DLBCL, it is unclear how survival has changed at the population level following its approval. Herein, we performed a population-based cohort study using the SEER-17 database. The primary exposure was a period of diagnosis (2014-2017 vs. 2018-2021), and these periods were selected based on the first FDA-approval of CAR-T in 2017. Study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). A total of 51,584 patients with DLBCL were included in the study with 24,861 patients diagnosed in time period-1 (2014-2017) and 26,723 patients diagnosed in time period-2 (2018-2021). The median age at diagnosis was 68 years (interquartile range, 57-77) and most patients were White (n = 42,190, 82%) with advanced stage at diagnosis (n = 28,203, 55%). In unadjusted analysis, the 5-year RS (95% CI) increased from 64% from 2014 to 2017 to 66% from 2018 to 2021, while 5-year OS increased from 54 to 55%, and 5-year LSS increased from 64 to 66%. On competing risks analysis, the 5-year probability of death from lymphoma decreased from 34 to 31%. The improvements in survival were observed across age, disease stage, and racial groups, and remained significant when adjusting for age, sex, race, stage, B symptoms and documented receipt of chemotherapy in multivariable survival models (adjusted OS HR = 0.97, 95%CI = 0.94-1.00, p = 0.04; adjusted LSS HR = 0.93, 95%CI = 0.90-0.96, p < 0.001). We found improved survival for patients with DLBCL diagnosed between 2018 and 2021 when compared to those diagnosed between 2014 and 2017. These findings will serve as the benchmark for future studies evaluating the impact of CAR-T administered earlier in their disease course.

PURPOSE/OBJECTIVE:The dermatological management of cancer patients with cutaneous adverse events occurring during and after oncologic treatment is known as supportive oncodermatology. This includes prevention, early identification, and mitigation of dermatologic toxicities. The aim of the international RESCUE (Residents' survey on training of dermatology residents in supportive oncodermatology) study was to ascertain the current level of expertise in supportive oncodermatology among dermatology residents. METHODS:The European Task Force "Dermatology for cancer patients" and the US Oncodermatology Society developed an online questionnaire with 30 multiple-choice items. Responses were collected using qualitative ordinal data (yes/no, 1-5 ratings) and multiple-choice options. Ordinal range results were analyzed by aggregating responses 1 + 2 + 3 versus 4 + 5, with 5 representing the highest grade ("extremely confident" or "full training"). RESULTS:A total of 442 dermatology residents from 20 countries replied. These participants reported receiving less comprehensive training in supportive oncodermatology (only 41% receiving complete training) compared to immunodermatology (75%), cutaneous oncology (75%), dermoscopy (64%), and dermatologic surgery (50%). Only 17% of the residents reported feeling confident in managing the dermatological toxicities associated with anticancer treatments. Residents also indicated receiving less education regarding toxicities related to endocrine therapies (28%). In particular, lower levels of competence were reported in managing nail, hair, and oral toxicities. A significant majority of residents (98%) deemed it essential to enhance training in dermatological toxicities associated with anticancer therapies during their oncology residency. CONCLUSION/CONCLUSIONS:The RESCUE study represents the first project assessing residents' education in supportive oncodermatology. To enable future generations of dermatologists to provide enhanced care for cancer patients, supportive oncodermatology training should be integrated in residency programs worldwide, corresponding to training in other subspecialties. A more practical approach should also be incorporated, including extended training in hair, nail, and oral toxicities, enhancing the competencies of dermatology residents in all countries.

BACKGROUND/UNASSIGNED:Patients with bicuspid aortic stenosis who receive transcatheter aortic valve replacement (TAVR) may require subsequent valve interventions in their lifetime; however, the feasibility of redo-TAVR in this population is uncertain. We aimed to assess redo-TAVR feasibility in bicuspid patients and develop a predictive virtual valve planning algorithm. METHODS/UNASSIGNED:We studied computed tomography scans of bicuspid patients who received a balloon-expandable transcatheter heart valve (THV) in the LRT trial (Low Risk TAVR). Redo-TAVR feasibility, determined by valve-to-coronary and valve-to-aorta measurements on 30-day computed tomography, was assessed according to raphe location and calcification. A virtual valve planning algorithm was developed using baseline and 30-day computed tomography scans. RESULTS/UNASSIGNED:<0.001) due to favorable shifting of the THV away from the coronary ostia. A bicuspid virtual planning algorithm accounting for 83.4% THV underexpansion, resulting in an 11.9% taller frame and translation of the THV away from the calcified raphe (mean valve shift 6.6 mm) achieved 86.7% sensitivity and 88.9% specificity for predicting redo-TAVR feasibility. CONCLUSIONS/UNASSIGNED:Calcified raphe in left/right cusp fusion shifts the THV away from the coronary ostia, reducing coronary obstruction risk during redo-TAVR. Underexpansion causing increased THV frame height and valve shifting is common in bicuspid patients; a virtual planning algorithm accounting for these aspects can accurately assess redo-TAVR risk. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02628899.

Background and ObjectivesWhile hearing loss is a known risk factor for dementia, the impact of incident hearing loss on subsequent dementia risk remains underexplored. This study examined the association between newly reported hearing loss and dementia risk in U.S. adults, focusing on critical intervention periods for dementia prevention.Research Design and MethodsParticipants from the Health and Retirement Study who reported no hearing loss or hearing aid use in 2010 or 2012 were included. Incident hearing loss and dementia were assessed via self-report and proxy report. Pooled logistic regression models with inverse probability weighting estimated the cumulative incidence of dementia at 2, 4, 6, and 8 years after baseline. Risk ratios (RR) with 95% confidence intervals were calculated from 200 bootstrap samples. Subgroup analyses were conducted by age, sex, and cardiovascular disease (CVD) status.ResultsAmong 13,599 participants, 1125 (8.3%) reported incident hearing loss. Dementia incidence was higher among those with hearing loss (6.6%) compared to those without (4.9%). Starting at 4 years, incident hearing loss was associated with a higher dementia risk, persisting at 8 years (RR = 1.34; 95% CI: 1.05, 1.59). This association was significant among individuals aged 50-64 years and those with CVD.Discussion and ImplicationsIncident hearing loss is associated with a heightened dementia risk, particularly in midlife and among individuals with CVD. Future research should investigate the effectiveness of timely interventions aimed at preventing dementia in individuals with hearing loss.

BACKGROUND:Despite recent improvements in radiation safety, interventionalists are increasingly exposed to radiation during cardiac catheterization laboratory (CCL) procedures. The RADPAD was designed as a protective scatter-radiation absorbing shield with the goal of reducing scatter radiation. Early studies demonstrated between a 20 and 62 % relative reduction in scatter radiation. The purpose of this study was to examine the impact of the RADPAD through a randomized controlled trial in a large contemporary CCL. DESIGN/METHODS:The ATTENUATE (v) Trial is an investigator-initiated, prospective, randomized controlled trial which will randomize 1000 CCL procedures 1:1 to use of the RADPAD vs. no use of the RADPAD. The primary outcome of interest is the most proximal operator's dose-area product (DAP)-normalized operator dose (E) defined as E divided by DAP. Additional subgroup analysis comparing types of procedure will also be performed. Every case will utilize contemporary radiation safety equipment. SUMMARY/CONCLUSIONS:The ATTENUATE Trial is the largest randomized controlled trial to evaluate the utility of the RADPAD in reducing relative operator exposure in a contemporary CCL including coronary and structural interventions.

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

BACKGROUND:Disruption of ambulatory healthcare in New York City (NYC) during the COVID-19 pandemic was common, but the impact on the cardiometabolic health of vulnerable patient groups is unknown. Therefore, we estimated the effect of total care disruption (TCD) on blood pressure (BP) control among older NYC residents with hypertension and at least one other chronic condition, and examined whether neighborhood poverty moderated this impact. METHODS:From the INSIGHT Clinical Research Network, we identified NYC residents ≥50 years of age with hypertension and at least one other chronic condition. TCD was defined as no ambulatory or telehealth visit during the pandemic. We contrasted the change in prevalence of controlled BP (BP <140/90) before and after the pandemic among those with and without TCD via an inverse probability weighted (IPW) difference-in-difference regression model. RESULTS:Among 212,673 eligible individuals, mean age was 69.5 years (SD: 10.2 years) and 15.1% experienced TCD. BP control declined from 52.4% to 45.9% among those with TCD and from 53.6% to 48.9% among those without TCD. After IPW adjustment, a larger decline in BP control was noted among those with TCD (adjusted difference-in-difference = 1.13 percentage points (95% CI 0.32-1.94, p-value=0.0058)). There was no consistent difference in the relationship between TCD and post-pandemic BP control across neighborhood poverty levels. CONCLUSION/CONCLUSIONS:COVID-19-related TCD was associated with a modest decline in BP control among older adults with hypertension in NYC; this was not moderated by neighborhood poverty level.

Idursulfase is the first-line and only available enzyme replacement therapy (ERT) for Mucopolysaccharidosis type II (MPS II), or Hunter Syndrome. Deficiency in the lysosomal enzyme iduronate-2-sulfatase leads to progressive skeletal deformities, neurologic deterioration, airway obstruction, and cardiomyopathy. In severe cases, these deformities can lead to death during teenage years (Stapleton et al. 2017). Continuous treatment with ERT is essential to prevent irreversible changes. However, 16 out of 108 (15%) patients had hypersensitivity reactions to idursulfase during clinical trials. Hypersensitivity reactions have also been reported several years into treatment (Elaprase 2018). Therefore, it is critical to evaluate for hypersensitivity reactions and desensitize patients to idursulfase. We report a fourteen-year-old male who was evaluated using a nonirritating skin test concentration and underwent a novel desensitization protocol for Lysosomal Storage Disease ERT.